Rhinovirus infection is a major cause of the common cold and an important trigger of disease exacerbations in children and adults with allergic asthma. Infections occur frequently owing to variability among the numerous serotypes of rhinovirus and the consequent barrier to mounting protective responses upon exposure to unrelated strains.
Human rhinovirus (RV) accounts for up to half of all adult cases of common cold. Children experience 8 to 12 infections annually, while the infection rate is lower in adults (˜2-3 per year). RV infection poses serious health risks among children and young adults with allergic asthma, by inducing disease exacerbations that are often severe. Moreover, RV has been implicated in the development of asthma in early childhood. Despite the enormous public health burden, there is no intervention to prevent RV infection. Notably, whereas asthma exacerbations can be prevented by blockade of IgE, this approach has major practical limitations. T-cell-based strategies to prevent RV infection would have the major advantage of conferring long-lasting protection in the first decades of life, when asthmatics are most susceptible to adverse respiratory sequelae.
Human rhinovirus is a single-stranded RNA virus of ˜7,200 bp belonging to the picornaviridae family. RV infection results in production of serotype-specific neutralizing serum antibodies at 1-2 weeks post-infection which can persist for a year. These antibodies confer protection from re-infection and reduce symptom severity upon experimental challenge with the same serotype. However, cross-neutralization among the more than 100 serotypes identified to date is limited owing to the high degree of variability among different RV strains. This results in frequent infections and poses a major challenge to vaccine development.
Activation of RV-specific CD4+ T cells is a critical antecedent to IgG responses. Despite this, little is known regarding the properties of CD4+ T cells that contribute to protection. This can be attributed, at least in part, to the lack of robust mouse models of RV infection, and to challenges in identifying and tracking rare RV-specific T cells in humans. Studies performed over 15 years ago reported the ability for RV-specific T cells cloned from tonsils or peripheral blood to be activated by either serotype-specific or cross-reactive epitopes.
Though earlier work implied that Th1 effector cells were integral to the protective response against RV, no studies formally tested this theory, which has since become dogma. It is now recognized that naïve CD4+ T cells develop into a variety of specialized T-cell subsets under the control of lineage-specifying transcription factors. These subsets include “conventional” effector (Teff) types (e.g., Th1, Th2 and Th17), as well as T follicular helper (Tfh) cells. Recent work in animal models indicates that Tfh cells, which provide help to B cells in germinal centers for antibody responses, persist as memory T cells following acute viral infection.
There is a long felt need in the art for compositions and method useful for preventing and treating Rhinovirus infections and for determining how to prevent and treat such infections. The present invention satisfies these needs.